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HIV-associated nephropathy: Protocol and rationale for an exploratory genotype-phenotype study in a sub-Saharan
Aminu Abba Yusuf1, Baba Maiyaki Musa2,3, Najibah Aliyu Galadanci4
1Department of Haematology and Blood Transfusion, Bayero University Kano/Aminu Kano Teaching Hospital, Kano, Nigeria.
Insights
This study identifies novel blood-based biomarkers for chronic kidney disease (CKD) in HIV-positive individuals of African descent. These findings pave the way for personalized medicine approaches in managing HIV-associated kidney disease.
Area of Science:
- Genetics and Genomics
- Nephrology
- Infectious Diseases
Background:
- HIV-positive individuals of African descent experience disproportionately high rates of chronic kidney disease (CKD) and progression to end-stage kidney disease (ESKD).
- Significant knowledge gaps exist regarding genetic susceptibility and the pathophysiology of CKD progression in this population.
- Understanding these factors is crucial for developing targeted interventions.
Purpose of the Study:
- To conduct an exploratory genotype-phenotype study in HIV-positive individuals with CKD in Nigeria.
- To identify blood-based differential gene expression biomarkers associated with different kidney risk categories.
- To lay the groundwork for future genome-wide association studies and personalized medicine.
Main Methods:
- Screening 150 HIV-positive adults for CKD using proteinuria and estimated glomerular filtration rate.
- Selecting 32 eligible participants into four KDIGO 2012 risk categories, matched for key clinical factors.
- Utilizing mRNA-sequencing (RNA-Seq) and reverse transcription quantitative polymerase chain reaction (RT-qPCR) to identify and validate differential gene expression markers.
Main Results:
- The study aims to provide valuable insights into potential differential expression biomarkers in HIV-associated kidney disease.
- Novel biomarkers will be identified across different CKD risk categories within a sub-Saharan African population.
- The findings will inform future population-based genome-wide association studies.
Conclusions:
- Validated biomarkers can serve as targets for developing stage-specific therapeutic interventions.
- This research supports the paradigm of precision medicine in managing HIV-associated kidney disease.
- Identifying genetic factors is key to advancing personalized treatment strategies.
Background:
HIV-positive persons of African descent are disproportionately affected by chronic kidney disease (CKD). Deterioration to end-stage kidney disease (ESKD) also occurs in this population at a higher frequency. There remains a lot to learn about the genetic susceptibility to CKD in HIV positive patients, and the pathophysiology of progression to ESKD.
Objectives:
We will conduct an exploratory genotype-phenotype study in HIV-positive persons with CKD in Aminu Kano Teaching Hospital, Nigeria, to determine blood-based differential gene expression biomarkers in different kidney risk groups according to the KDIGO 2012 criteria.
Methods:
We will consecutively screen 150 HIV-positive adults (≥18 years of age) attending the HIV clinic of Aminu Kano Teaching Hospital, Kano, Nigeria, for CKD based on proteinuria and elevation of estimated glomerular filtration rate. Among these, two separate groups of 16 eligible participants each (n = 32) will be selected in the four (4) KDIGO 2012 kidney risk categories. The groups will be matched for age, sex, viral suppression level and antiretroviral (ARV) regimen. In the first group (n = 16), we will determine differential gene expression markers in peripheral blood mononuclear cells using mRNA-sequencing (RNA-Seq). We will validate the differential expression markers in the second group (n = 16) using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Using a systems-based approach, we will construct, visualize and analyze gene-gene interaction networks to determine the potential biological roles of identified differential expression markers based on published literature and publicly available databases.
Results:
Our exploratory study will provide valuable information on the potential roles of differential expression biomarkers in the pathophysiology of HIV-associated kidney disease by identifying novel biomarkers in different risk categories of CKD in a sub-Saharan African population. The results of this study will provide the basis for population-based genome-wide association studies to guide future personalized medicine approaches.
Conclusion:
Validated biomarkers can be potential targets for the development of stage-specific therapeutic interventions, an essential paradigm in precision medicine.
